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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review of the action of estrogens and progestagens, the steroids in oral contraceptives, on cells in the endometrium, breast, ovary, cervix and other tissues, regarding possible causative role in cancer development focuses on the level of steroid receptors and observed actions of these hormones on the cellular level. The steroid hormones are thought to interact with cells by binding to a specific receptor on the cell surface, especially estrogen receptors, while progestagen receptors overlap with glucocorticoids and androgens. Oral contraceptives typically have progestin dosages at the plateau of the dose-response curve, but lower estrogen doses may possible improve the cancer risk. Plasma levels are not reliable estimates of estrogen influence; moreover, estrogens are synthesized locally. Carcinogenesis is a multi-stage process requiring cell proliferation, involving an initiating event, and probably promotion agents, resulting in tumor growth. Estrogens increase cell replication in endometrium, and progestins counter it. Breast cancer evolves in several cell types in the epithelium of the terminal ductal lobular unit, with a 20-year latency. Estrogens stimulate ductal growth and progestins its development, and both are required for full stimulation, as in pregnancy. Estrogens usually stimulate cancer growth, but the precise sensitivity to steroids depends on the timing in the life cycle of the tumor. Ovarian cancer is unique in that neoplasms arise from the epithelium, not the hormone-sensitive tissue. Therefore the suppressive effect of steroids on ovarian neoplasia is thought to be via down- regulation of the gonadotropins, prevention of follicular rupture and consequent cell division of the epithelium, or some effect on growth regulating factors. The effect of steroids on the cervix is unclear, since cervical cancers are hormone-resistant, but there may be a step in transformation by human papilloma virus that involves a glucocorticoid- or progesterone receptor. Steroid receptors are also known to exist in tumors of liver, skin, colon, kidney and anterior pituitary, but their function is neoplasia is unknown.
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PMID:Biology of female sex hormone action in relation to contraceptive agents and neoplasia. 165 Dec 4

Transforming growth factor-alpha (TGF-alpha) is frequently coexpressed with its receptor, epidermal growth factor receptor (EGF-R), in several types of carcinoma and sarcoma. It is believed that this results in an autocrine stimulation of tumor growth in these tumors. We have found that TGF-alpha and EGF-R/c-erbB RNAs were co-expressed at significantly higher levels in papillary thyroid carcinomas and their lymph-node metastases than in non-neoplastic thyroid tissues. We also observed a low level of expression of RNA specific for insulin-like growth factor I in these tumors, which was highest in a lymph-node metastasis. Autocrine stimulation by TGF-alpha may thus be a common feature of papillary carcinomas of the thyroid. Since EGF is known to induce proliferation and dedifferentiation of normal thyroid cells in culture, TGF-alpha and its receptor may play an important role in thyroid carcinogenesis.
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PMID:Co-expression of the genes encoding transforming growth factor-alpha and its receptor in papillary carcinomas of the thyroid. 169 67

We demonstrate in this study that infection with Moloney murine leukemia virus (M-MLV) and exposure to 3-methylcholanthrene (3-MC) can cooperate to transform NIH/3T3 mouse fibroblasts. M-MLV seems to stimulate the expression of c-myc and of a certain major histocompatibility complex (MHC) class I gene. Yet M-MLV infection by itself is insufficient to transform these cells. However, exposure of the infected cells to 3-MC resulted in a rapid cell transformation with concomitant enhancement of c-Ha-ras and H-2K class I MHC gene expression in the transformed cells. No such transformation was observed when uninfected NIH/3T3 cells were similarly treated with this carcinogen. Clones of cells transformed by this combined effect of M-MLV and 3-MC were found to be highly tumorigenic in fully immunocompetent allogeneic BALB/c mice. We provide evidence to suggest that the enhanced expression of the H-2K gene in these transformed cells plays an important role in overcoming the BALB/c allogeneic barrier and allowing tumor growth in these mice.
Carcinogenesis 1990 Dec
PMID:Chemical-retroviral cooperative carcinogenesis and its molecular basis in NIH/3T3 cells. 170 67

alpha-Difluoromethylornithine (DFMO) treatment has been shown to modify carcinogenesis in many experimental tumor models, including breast, urinary bladder, and colon. This study was designed to determine whether DFMO treatment can inhibit tumor growth on chemical-induced colon cancer in rats. Effectiveness of DFMO in combination with mitomycin C (MMC) was also evaluated. Forty-two Sprague-Dawley rats received dimethylhydrazine (20 mg/kg) s.c. once weekly for 20 wk to induce colon cancer. Then a double-contrast barium enema was performed, and colon tumors were detected. The animals were divided into four groups that were subjected to the following treatment: none; DFMO alone; MMC alone; and a combination of DFMO plus MMC. After 5 wk of treatment, the barium enema was repeated. For the evaluation of treatment efficacy, tumor doubling time was adopted. The mean tumor doubling time in the control group was 20.7 +/- 9.1 days (SD). "Response" was judged as effective when tumor doubling time in treatment groups was more than 38.9 days, calculated from the mean + 2 SDs in the control group. Response rates in the DFMO, MMC, and DFMO plus MMC groups were 40.0%, 10.0%, and 82.3%, respectively. DFMO was a more effective inhibitor of tumor growth than MMC, and DFMO in combination with MMC resulted in a synergic diminution of tumor growth. The double-contrast barium enema is useful to observe sequential tumor growth and may be appropriate for the evaluation of new treatment on experimental colon cancer in rats.
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PMID:Reduced growth rate of dimethylhydrazine-induced colon tumors in rats. 173 57

The N-methyl-N-nitrosourea (NMU) model of hormone-responsive rat mammary carcinogenesis was used to address the hypothesis that melatonin (Mel), the principle hormone of the pineal gland, inhibits tumorigenesis by acting as an anti-promoting rather than an anti-initiating agent. Daily late-afternoon injections of Mel (500 micrograms/day), restricted to the initiation phase of NMU mammary tumorigenesis, were ineffective in altering tumor growth over a 20-week period. When Mel treatment was delayed for 4 weeks after NMU and then continued through the remainder of the promotion phase, only tumor number was significantly lower than in controls. However, when Mel injections encompassed the entire promotion phase, both tumor incidence and number were significantly lower than in the controls. Although elimination of the endogenous Mel signal via pinealectomy promoted tumor growth, the effect was not statistically significant. Serum levels of estradiol and tumor estrogen receptor content were unaltered by either Mel or pinealectomy. While Mel treatment failed to affect circulating prolactin levels, pinealectomy caused a two-fold increase in serum prolactin. The estradiol-stimulated recrudescence of tumors following ovariectomy was completely blocked by either 20, 100 or 500 micrograms Mel/day or tamoxifen (20 micrograms/day). Thus, Mel appears to be an anti-promoting hormone that may antagonize the tumor-promoting actions of estradiol in this model of mammary tumorigenesis.
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PMID:Pineal melatonin inhibition of tumor promotion in the N-nitroso-N-methylurea model of mammary carcinogenesis: potential involvement of antiestrogenic mechanisms in vivo. 174 57

Several polypeptide hormones have been demonstrated to stimulate or inhibit cell division in the cells of the pancreas. Therefore, receptors for these hormones have been sought in pancreatic carcinomas, and several examples have been reported. In some instances, stimulation of tumor growth by the corresponding peptide has been demonstrated or growth was blocked by a receptor antagonist. Receptors and binding proteins for steroid hormones also have been reported in carcinomas of the pancreas. In experimental carcinogenesis, the growth of preneoplastic lesions and incidence of neoplasms have been influenced by both peptide and steroid hormones in some species. Experimental manipulation of sex steroid hormones has yielded both inhibition and enhancement of growth of human and rat pancreatic cancers, but thus far, clinical trials have failed to document advantageous approaches for steroid or antihormonal therapy. These observations imply that trophic or growth-inhibiting polypeptide and steroid hormones may serve as promoters or inhibitors of carcinogenesis in the pancreas, and may influence the growth of established carcinomas. Receptor blockers may provide a clinical approach for slowing the growth of some cancers.
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PMID:Hormones and pancreatic cancer. 174 51

Expression of protooncogenes c-myc, N-myc, c-fos, Ha-ras 1, Ki-ras 2, yes, abl, src, N-ras, met and mos was studied in human gastric tumors and in rat gastric mucosal membrane during gastric carcinogenesis induced in rats by means of N-methyl-N'-nitro-N-nitroso guanidine (MNNG). Elevated expression of protooncogenes c-myc, c-fos, Ha-ras 1, Ki-ras 2, N-myc and Raf 1 was observed in carcinomas of human stomach. Amplification of Ha-ras 1 protooncogene was found in the human gastric tumor and metastasis. Point mutation was not detected in 12 the codon of Ha-ras I protooncogene. Expression of these protooncogenes was not altered during gastric carcinogenesis induced by MNNG in rats. However, within early steps of cancerogenesis (9 days, 3 months) amplification of ribosomal genes occurred in rat gastric mucosal membrane and in adenocarcinoma developed, while the tumor growth was accompanied by activation of mitochondrial genes.
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PMID:[Biochemical and molecular biological aspects of stomach cancer development in human and animal]. 181 23

We have reviewed retrospectively the records of 157 patients, less than or equal to 30 years of age with nasopharyngeal carcinoma (NPC) from 218 such cases identified in the tumor registry files of three major teaching hospitals in Taipei, Taiwan. These cases were diagnosed between 1 January 1982 and 31 December 1985, with a minimum follow-up of 2 years. The average age was 25, with a male/female ratio of 1.67. The TNM (tumor size, nodes, metastases) classification of 127 patients showed T1, 22%; T2, 33.1%; T3, 23.6%; T4, 21.3%; N0, 26%; N1, 16.5%; N2, 27.6%; N3, 30%; and M1, 13.4%. Antibody titer to Epstein-Barr virus capsular antigen (EBVCA) were elevated in 45 of 48 patients tested. Of the 29 patients who had hepatitis B (HB) viral survey done 34.5% were positive for HB surface antigen (HBsAg). Of 13 patients with elevated EBVCA antibody who were also tested for HB, six were HBsAg carrier. Actuarial survival rates of 2 and 3 years are 70 and 62%, respectively, among the 90 patients who were followed regularly or to death. HBsAg carriers and patients with M1 disease had a shorter survival time. We concluded that patients less than 30 years of age seemed to have an increased incidence of NPC, compared to that in an earlier report. Our patients frequently presented with advanced stage and poor prognosis. The high rate of HB carrier raises the possibility that HBV may play a role in the carcinogenesis and tumor growth in some NPC patients. Future prospective studies are needed.
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PMID:Nasopharyngeal carcinoma in young patients. 184 56

Results from epidemiological studies have generally indicated an association of dietary saturated animal fats with human breast cancer risk. Some studies, however, have suggested a similar association for some polyunsaturated vegetable fats shown to promote both rodent mammary carcinogenesis and metastasis. This study was performed to evaluate the effects of corn oil on growth and metastasis of MDA-MB-435 human breast cancer cells, which have a propensity for metastasis. Corn oil is rich in the omega-6 fatty acid linoleic acid. Fifty-eight female athymic nude mice (NCr-nu/nu) were fed a high-fat diet (23% wt/wt corn oil; 12% linoleic acid) or a low-fat diet (5% wt/wt corn oil; 2.7% linoleic acid). Seven days after diets were started, tumor cells (1 x 10(6) were injected into a mammary fat pad. The time to appearance of solid tumors and the tumor size were recorded. After 15 weeks, the study was terminated, and autopsies were performed to determine the weight of the primary tumor and the extent of metastasis. The latent interval for tumor appearance in the animals fed the high-fat diet was shorter than that in the low-fat diet group, and the tumor growth rate in the high-fat diet group showed a small but statistically significant increase compared with the low-fat diet group. Primary tumors developed in 27 of the 29 mice on the high-fat diet and in 21 of the 29 on the low-fat diet. Of the mice with palpable primary tumors, 18 of 27 in the high-fat diet group and eight of 21 in the low-fat diet group had macroscopic lung metastases. The extent of metastasis in the high-fat diet group was independent of the primary tumor weight, but only those in the low-fat diet group with primary tumors weighing more than 2 g developed metastases. These results suggest that a high-fat diet rich in omega-6 polyunsaturated fatty acid can enhance metastasis of human breast cancer cells in this mouse model. The findings support the need for further study of the relationship between dietary polyunsaturated fats and breast cancer risk and for experiments to determine the effect on metastasis of only a 50% difference in fat intake--the dietary goal of the proposed clinical trials of low-fat dietary intervention in breast cancer patients.
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PMID:Effect of dietary fat on human breast cancer growth and lung metastasis in nude mice. 173 78

One-week-old male and female mice of the A, BALB/c (C), and C3H/He (C3) strains and of the AC3 and CC3 F1 hybrids were treated with a single dose (300 mg/kg s.c.) of urethan and then kept without further treatment until 30 and 40 weeks (males) or 30 and 65 weeks (females). The degree of difference in susceptibility to hepatocarcinogenesis between the susceptible C3 and the resistant A and C mice, in the different age and sex groups, was 4-12-fold by the analysis of the number of nodules/cm3 (N/cm3), which represents an estimation of tumor frequency and was more than 400-fold as indicated by the percentage of liver volume occupied by nodules (V%), an estimation of tumor size. With regard to lung carcinogenesis, mice of the A strain proved 5-10- and 20-70-fold more susceptible than the C and the C3 mice, respectively, as indicated by the number of microscopically identified lung tumors/mouse (N), an estimation of tumor frequency. The lung tumor size, as estimated by the mean tumor volume (V), was similar in A and C mice but much higher in the A than in the C3 groups (13- approximately 1000-fold difference). The AC3 hybrid was highly susceptible to both liver and lung carcinogenesis. The CC3 hybrid was as susceptible to lung carcinogenesis as its C parent and had an intermediate susceptibility to hepatocarcinogenesis. Our results indicate that a major determinant in the genetic susceptibility to hepatocarcinogenesis, and perhaps to lung carcinogenesis too, is tumor growth, as evidenced by a much greater tumor size in genetically susceptible than resistant mice.
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PMID:Quantitative analysis of genetic susceptibility to liver and lung carcinogenesis in mice. 193 90


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